Ketones, p-chlorovinyl

Acylation of acetylenic compounds provides /ra/ j -P-chlorovinyl ketones (181). Vinyl cations were proposed to be the intermediates in these reactions. 

Alkynes are readily acylated with acid chlorides under Friedel-Crafts conditions to form, in most cases, fram-p-chlorovinyl ketones through the corresponding vinyl cation intermediate [Eq. (8.16)]. The first study in 1935 reported low yields.11 Later in acylations with acyl triflates, p-keto vinyl triflates were obtained in satisfactory yields.123 When aroyl derivatives are used, the intermediate can undergo cyclization to form indenones. Chlorovinyl ketones formed from terminal alkynes may also react further losing hydrogen chloride to yield conjugated acetylenic ketones 11,13... 

Acetylene was passed into a stirred solution of 3.05 grams (0.44 mol) of lithium in 300 ml of liquid ammonia until the blue color exhibited by the mixture had disappeared. Ethyl p-chlorovinyl ketone (47.4 grams 0.40 mol) dissolved in 50 ml dry ether was then added to the resulting solution of... 

Dihydropyrones are valuable intermediates for the synthesis of a variety of substituted tetrahydropyran rings. Recently, stereoselective aldol reactions of p-chlorovinyl ketones using the dienol boronate derivative derived from chiral IpC2BOTf was utilized for enantioselective formation of dihydropyrones. No detectable racemization was reported on the cyclization step (eq 4). ... 

Pudovik, A.N., Nikitina, V.L, and Kurguzova, A.M.. Reactions of organophosphorus compounds containing active methylene groups with methyl P-chlorovinyl ketone and a-halo ethers, Zh. Obshch. Khim., 40, 291, 1970 J. Gen. Chem. USSR (Engl. Transl.), 40, 261, 1970. 

The Friedel-Crafts acylation of alkynes is an extremely rapid reaction, and usually leads to the formation of the f/ flni-P-chlorovinyl ketone (equation 23). Reaction temperatures can be as low as -70 °C. The reaction proceeds via reaction of the acyl halide-Lewis acid complex with the alkyne, and whilst the implied vinyl cation has not been observed directly, the reaction products can be understood in terms of reaction of such an intermediate with nucleophiles, usually halide ion. Whilst the r/-an.r-chlorovinyl ketone has been described as the sole product of the reaction by some workers, others have reported the formation of mixtures of the cis and trans forms, under conditions that did not appear to lead to isomeriza-... 

Hydrochlorination Addition of hydrochloric acid to ynones in the presence of FeS04 is stereoselective, the products from l-aryl-2-propyn-l-ones being predominantly ( )-P-chlorovinyl ketones. 

Oxazinium salts 30 are the 3-aza analogues of pyrylium salts. They are obtained by cyclocondensation of P-chlorovinyl ketones with nitriles or by cyclocondensation of alkynes with N-acylmethanimidoyl chlorides catalysed by SnC ... 

Successful variations on this theme include the use, as synthons for the 1,3-dicarbonyl component, of P-chlorovinyl ketones, or conjugated alkynyl aldehydes. ... 

The lack of favorable overlap with the carbonyl t-system makes the a-vinyl deprotonation challenging. However, once a non-planar conformation is enforced, the situation changes dramatically. This is illustrated by facile a-vinyl enoUzation of (E)-p-chlorovinyl ketones by abase as weak as EtjN. The mild a-vinyl enoUzation of these compounds was suggested to originate from their non-planar conformation which, unlike the planar conformation of respective (Z)-isomers, leads to a good orbital overlap between the carbonyl rt-system and the a-C-H bond. The enolization to aUenol is preferred over the a-C(sp )-H bond deprotonation from R. 

Kim, H. Y, Li, J-Y, Oh, K. (2013). A Soft Vinyl Enolization Approach to a-Acylvinyl Anions Direct Aldol/Aldol Condensation Reactions of (E)-P-Chlorovinyl Ketones. Angewandte Chemie International Edition, 52, 3736-3740. 

Scheme 6.12 Preparation of p-chlorovinyl ketones VIII in ionic liquid...

Bridgedhead thiazolo[3,2-a]pyrimidines, and their isosteres occupy a unique place in medicinal chemistry due to their wide application as drug and drug-intermediates [7-11]. Several methods are known for synthesis of thiazolo[3,2-a]pyrimidine derivatives, from 2-mercaptopyrimidines and a-halo ketones, and by cyclocondensation of a-aminothiazoles with P-diketones, P-keto aldehydes, and their acetals, P-chlorovinyl ketones and aldehydes. 

The preparation of alkoxyethynyl alcohols from ketones and ethoxyacetylene. In the Isler modification the tedious preparation of ethoxyacetylene is obviated by treating p-chlorovinyl ether with lithium amide to yield lithium ethoxyacetylene, which is then condensed with the ketone ... 

As primary step, a (formal) vinyl substitution of chlorine in 24 takes place consisting of Michael addition of thiolate and concomitant elimination of HCI. The intermediate 25 cyclizes by intramolecular aldol condensation to give 26. P-Chlorovinyl aldehydes (24) are prepared from a-methylene ketones by reaction with DMF/POCI3 (Vilsmeier-Haack reaction). 

Acetylation of Alkynes. Under Friedel-Crafts conditions (AcCl/AlCL, CCI4, 0-5 °C), acetylene undergoes acetylation to afford p-chlorovinyl methyl ketone in 62% yield and under similar conditions (AcSbF, MeN02, —25 °C) 5-decyne undergoes acetylation to afford 6-acetyl-5-decanone in 73% yield. ... 

In another three-component process, 1-chlorovinyl p-tolylsulfoxidcs 181 are first prepared from ketones (Scheme 5.27) [71]. 

A dry 1-1. three-necked flask fitted with a mercury-sealed stirrer, a calcium chloride drying tube, and a 500-ml dropping funnel, protected by a calcium chloride drying tube, is surrounded by an ice-salt mixture at —11° Anhydrous methanol (130 ml) (Notes 1 and 2) and 161 g (1 mole) of /3-chlorovinyl isoamyl ketone (p 27) are poured into the flask (Note 3). A solution of 43 g (1 04 moles) of sodium hydroxide (97%) and 350 ml of absolute methanol (Note 4) is added dropwise with stirring over a period of 2 hours, during which time the bath temperature is kept between —11° and —8°... 

A very interesting synthetic method of bicyclo[n.l.O]alkanes from cychc ketones via this 1,3-C,H insertion of magnesium carbenoid as a key reaction was reported (equation 22) . 1-Chlorovinyl p-tolyl sulfoxide (76) was synthesized from cyclopentadecanone and chloromethyl p-tolyl sulfoxide in three steps in high overall yield. Lithium enolate of tert-butyl acetate was added to 76 to give the adduct 77 in quantitative yield. a-Chlorosulfoxide (77) in a toluene solution was treated with i-PrMgCl in ether at —78 °C and the reaction mixture was slowly warmed to 0°C to afford the bicyclo[13.1.0]hexadecane derivative 79 in 96% yield through the reaction of the intermediate magnesium carbenoid 78. 

Stereochemistry of this reaction is also quite interesting. Thus, both geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides (165-167) were synthesized from 2-cyclohexenone, methyl vinyl ketone and 2-heptanone respectively, and the corresponding magnesium alkylidene carbenoids were generated and treated with A-lithio aniline or A-lithio 1-aminonaphthalene. The results are summarized in Table 9. 

On the other hand, when this reaction was carried out with 1-chlorovinyl p-tolyl sulfoxide derived from unsymmetrical dialkyl ketone 167 with Af-lithio 1-aminonaphthalene (entries 7 and 8), Z-ortho-alkenylated arylamine Z-171 was obtained as the main product from both vinyl sulfoxides with low stereoselectivity. The stereospecificity and stereoselectivity mentioned above are explained from the high configurational stability of the magnesium carbenoids generated from 1-chlorovinyl p-tolyl sulfoxides derived from a,/ -unsaturated ketones. 

This reaction was first reported by Arens et at. in 1947. It is the synthesis of a,p-unsaturated aidehyde from the reaction of ethoxyethynemagnesium bromide and ketone or aidehyde and is known as the Arens and van Dorp reaction. Because the preparation of ethoxyacetyiene is tedious, this reaction has been modified to generate lithium ethoxy-acetylene by treatment of /3-chlorovinyl ether with lithium amide, which then reacts with a ketone or aldehyde to form a,/3-unsaturated aldehyde. This new protocol is referred to as the Isler modification. 

Ketene S,lV-acetals are usually attacked by electrophilic reagents at the P-carbon, yielding iminium salts, thus ketene 5,7V-acetals have been alkylated and acylated. Similar reactions are described with chlo-roformic acid esters, cyanuric chloride, wj-nitrophenylsulfenyl chloride, 2,4-dinitrochlorobenzene, 3-chloro-2-cyanoacrylonitriles and 2-chlorovinyl phenyl ketone. Usually it is not the initially formed iminium compounds but the substituted ketene 5,A -acetals which are isolated, e.g. (120) and (121 Scheme 12). ... 

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